A greater proportion of patients who arrive at the hospital in the
first 60 minutes after symptom onset ¡X the so-called "golden hour" ¡X
receive thrombolytic therapy than those who arrive later, new data
from the Get With The Guidelines-Stroke (GWTG-S) quality-improvement
program shows.

In this analysis, 12% of all ischemic stroke patients seen at 100
GWTG-S hospitals arrived within 1 hour of symptom onset, and 27.1% of
these were treated with tissue plasminogen activator (tPA) vs 12.9%
of those arriving between 1 and 3 hours after onset.

However, Jeffery L. Saver, MD, from the University of California, Los
Angeles Stroke Center, pointed out that golden-hour patients also had
door-to-needle (DTN) times that were about 20 minutes longer than
those arriving later, and only about 20% were treated within 60
minutes of arrival.

"These findings support greater public-education efforts to increase
the proportion of patients arriving in the first 60 minutes after
symptom onset and a revamping of our hospital's performance-
improvement activities to shorten the DTN times in patients who've
done their part in arriving in the first 60 minutes, to make sure we
do our part and get drug started for them in the next 60 minutes,"
Dr. Saver concluded.

He presented their findings here at the American Stroke Association
International Stroke Conference 2009.

Benefit Strongly Time Dependent

The benefit of intravenous (IV) tPA in acute ischemic stroke is
strongly time dependent, Dr. Saver said. Therapeutic yield of
treatment is maximal in the first minutes after stroke and declines
steadily during the first 3 hours. "Every minute that goes by without
treatment, 2 million nerve cells die," he said. "Every 10 minutes
that goes by without tPA, 1 fewer patient experiences benefit from
tPA."

Patients who present within the first 60 minutes after symptom onset
have the greatest opportunity for benefit from treatment, but these
patients have not been well characterized. "That's why we undertook
this study," Dr. Saver said.

They used the GWTG-S registry, a national database of acute strokes
treated at participating hospitals in the United States. From 905
participating hospitals, a total of 517,000 stroke and transient
ischemic attack patients were entered in the database between April
2003 and December 2007. After excluding those who did not arrive
directly at the emergency department by ambulance or private vehicle,
those having hemorrhagic strokes, and patients for whom a time of
symptom onset could not be documented, they were left with 106,924
patients for this analysis.

Of these, 28.3% arrived at the hospital within 60 minutes of symptom
onset; the mean onset-to-door time for these patients was 39.9
minutes.

Although most patient characteristics examined were to some extent
statistically significant, 2 factors stood out; National Institutes
of Health Stroke Scale (NIHSS) score, which was higher in those
arriving earlier (8 for those arriving within 60 minutes vs 4 in
those arriving after 3 hours), and arrival by ambulance, which was
the case in 79% of those arriving in the golden hour, vs 55% of those
arriving after 3 hours.

Overall, 11.8% of all ischemic stroke patients arriving directly at
the hospital with a documented onset time were treated with IV tPA,
vs 5% of those without a documented onset of symptoms. The mean onset-
to-door time in patients who received tPA was 56 minutes, and the
mean DTN time was 84 minutes.

Those arriving within the golden hour were much more likely than
those arriving later to receive thrombolysis, Dr. Saver said.

The frequency of delivery of tPA was 27.1% of the golden-hour
patients vs 12.9% in the 1-to-3 hour patients (P < .0001).

However, those arriving earlier also had longer DTN times. Patients
who arrived at the hospital within the first hour had a mean DTN time
of 90.6 minutes, compared with 76.7 minutes for those arriving
between 1 and 3 hours after symptom onset. Only 18.3% of these
patients who arrived within 60 minutes of symptom onset had a DTN
time under the recommended target of 60 minutes.

There was a "modest increase" of about 1.2% per year over time in the
number of golden-hour patients being treated within 60 minutes, from
12.8% in 2003 to 19.5% in 2007; this improvement did not appear to be
related to length of participation in the GWTG-S program, he noted.

Having More Time Should Not Mean Taking More Time

After his presentation, Dr. Saver was asked about what might explain
the longer times to treatment among those who arrived earlier.
Although they plan to look at this issue further in this data set, he
pointed out that doctors might take the opportunity for a longer
informed-consent process when they have more time.

Furthermore, during a press conference here, Dr. Saver speculated
that this potential problem of using the time for deliberation may
worsen over time, given the results of ECASS 3 reported last fall
that showed thrombolytic therapy was safe and effective up to 4.5
hours after symptom onset.

"I think for the providers, focusing the attention on how well your
health system is performing by focusing on door-to-needle time for
treatment, rather than the onset-to-treatment time or the maximal
permitted time, is the way to go," Dr. Saver said. "We're trying to
emphasize a door-to-needle time of 60 minutes."

Arthur Pancioli, MD, professor and vice chair of emergency medicine
at the University of Cincinnati, in Ohio, moderated a press
conference here where this paper was presented. He pointed out that
while there is a benefit to treatment, there are also serious risks
associated with thrombolytic therapy, including a 6.4% risk of
hemorrhage, "even if you're doing it right."

While it is still clearly the right thing to do, he said, "that would
give you pause . . . but what you cannot do is pause, and that's the
hard part.

"We're caught in a situation where you have to be fast, and you have
to do it well."